Clinical outcomes and prognostic factors associated with internal ureteral stent placement for malignant extrinsic ureteral obstruction.

PURPOSE: The optimal management of malignant extrinsic ureteral obstruction (MUO) remains unclear. It is necessary to assess the patient prognosis in deciding the adaptation of drainage of renal pelvis. In this study, we investigated the clinical outcomes after ureteral stenting for MUO and the predictive factors for overall survival in order to create a risk-stratification model. METHODS: We retrospectively analyzed the clinical and laboratory data of 93 patients with radiologically significant hydronephrosis associated with MUO who underwent successful stent placement between May 2005 and May 2018. RESULTS: The median survival duration after the initial stent insertion was 266 days. Of the 93 patients, 70 died, and the median interval from the first stent insertion to death was 160 days. Multivariate analysis showed that gastric cancer as the primary disease, poor performance status before stenting, and treatment after stent insertion were significant predictors of survival. According to these three factors, we stratified patients into the following four prognostic groups: no-factor (43 patients), one-factor (23 patients), two-factor (23 patients), and three-factor (4 patients) groups. This classification was effective for predicting survival, and the median survival durations in these groups were 807, 269, 44, and 12 days, respectively (p < 0.001). CONCLUSIONS: Our stratification model of patients with a poor prognosis after ureteral stent placement for MUO may allow urologists and clinicians to identify patients who will benefit from ureteral stenting.

First-in-human phase I clinical trial of the NY-ESO-1 protein cancer vaccine with NOD2 and TLR9 stimulants in patients with NY-ESO-1-expressing refractory solid tumors.

Cholesteryl pullulan (CHP) is a novel antigen delivery system. CHP and New York esophageal squamous cell carcinoma 1 (NY-ESO-1) antigen complexes (CHP-NY-ESO-1) present multiple epitope peptides to the MHC class I and II pathways. Adjuvants are essential for cancer vaccines. MIS416 is a non-toxic microparticle that activates immunity via the nucleotide-binding oligomerization domain 2 (NOD2) and TLR9 pathways. However, no reports have explored MIS416 as a cancer vaccine adjuvant. We conducted a first-in-human clinical trial of CHP-NY-ESO-1 with MIS416 in patients with NY-ESO-1-expressing refractory solid tumors. CHP-NY-ESO-1/MIS416 (µg/µg) was administered at 100/200, 200/200, 200/400 or 200/600 (cohorts 1, 2, 3 and 4, respectively) every 2 weeks for a total of 6 doses (treatment phase) followed by one vaccination every 4 weeks until disease progression or unacceptable toxicity (maintenance phase). The primary endpoints were safety and tolerability, and the secondary endpoint was the immune response. In total, 26 patients were enrolled. Seven patients (38%) continued vaccination in the maintenance phase. Grade 3 drug-related adverse events (AEs) were observed in six patients (23%): anorexia and hypertension were observed in one and five patients, respectively. No grade 4-5 drug-related AEs were observed. Eight patients (31%) had stable disease (SD). Neither augmentation of the NY-ESO-1-specific IFN-γ-secreting CD8+ T cell response nor an increase in the level of anti-NY-ESO-1 IgG1 was observed as the dose of MIS416 was increased. In a preclinical study, adding anti-PD-1 monoclonal antibody to CHP-NY-ESO-1 and MIS416 induced significant tumor suppression. This combination therapy is a promising next step.

Ureteral stents for malignant extrinsic ureteral obstruction: outcomes and factors predicting stent failure.

BACKGROUND: This study investigated the clinical outcomes of stent placement for malignant extrinsic ureteral obstruction (MUO) and predictive factors for stent failure. METHODS: We retrospectively analyzed clinical data for 91 patients with radiologically significant hydronephrosis due to MUO who underwent successful stent placement. In total, 132 ureters were stented for the decompression. Factors related to stent failure were analyzed with a Cox proportional hazards model. RESULTS: Stent failure occurred in 25 ureters in 20 patients. The median interval to failure was 63 days. The multivariate analysis showed that the significant predictors of stent failure were bladder invasion and severe hydronephrosis before the stent insertion. The patients were divided into three groups based on these two factors: low-risk (neither factor; 85 patients), intermediate-risk (one factor; 37), and high-risk (both factors; 10). The median stent failure-free survival rate at 3 months was 94.8% in the low-risk, 71.8% in the intermediate-risk and 55.6% in the high-risk group, respectively. Of the ureters with stent failure, there was successful re-replacement of internal stents in 3 low-risk, 6 intermediate-risk and no high-risk ureters. Replacement by nephrostomy was done in 2 low-risk, 5 intermediate-risk and 7 high-risk ureters. CONCLUSION: The patients considered at low-risk could be managed without stent failure by internal stenting. However, the patients at high-risk may require the consideration of nephrostomy or other alternatives as the initial treatment. Our stratification model may allow better risk stratification for patients with regard to ureteral stenting, helping to identify patients for whom ureteral stenting is indicated.

[The Predictive Factors of Stent Failure in the Treatment of Malignant Extrinsc Ureteral Obstruction Using Internal Ureteral Stents].

In this study, we retrospectively reviewed the experiences at our single institute in the treatment of malignant extrinsic ureteral obstruction (MUO) using ureteral stents to investigate the clinical outcomes and the predictive factors of stent failure. In 52 ureters of 38 patients who had radiologically significant hydronephrosis due to MUO, internal ureteral stents (The BARD(R) INLAY(TM) ureteral stent set) were inserted. The median follow-up interval after the initial stent insertion was 124.5 days (4-1,120). Stent failure occurred in 8 ureters (15.4%) of the 7 patients. The median interval from the first stent insertion to stent failure was 88 days (1-468). A Cox regression multivariate analysis showed that the significant predictors of stent failure were bladder invasion. Based on the possibility of stent failure, the adaptation of the internal ureteral stent placement should be considered especially in a patient with MUO combined with bladder invasion.

[A Case of Emphysematous Cystitis with Bladder Diverticulum].

Emphysematous cystitis (EC) is a rare form of acute complicated urinary tract infection (UTI). We report a case of EC with bladder diverticulum. A 77-year-old man who had a medical history of diabetes mellitus was admitted to our hospital with the chief complaint of macrohematuria and pneumaturia. Based on the findings of an abdominal computed tomography and cystoscopy, the diagnosis of EC and bladder diverticulum was made with its characteristic feature being gas within the bladder wall and lumen and a cystic lesion from the bladder. His condition improved immediately with a combination of bladder drainage and appropriate antibiotics. The cystography revealed a very large diverticulum causing incomplete bladder emptying and stagnation of urine. We considered diabetes mellitus and a large amount of residual urine after urination due to bladder diverticulum and neurogenic bladder as the possible causal factors of EC in this case.

[First 25 cases of photo-selective vaporization of the prostate (PVP) with 120-watt high performance system for benign prostatic hyperplasia].

PURPOSE: We examined the safety and efficacy of photo-selective vaporization of the prostate (PVP) using a 120-W high-performance system (HPS) for benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: We prospectively reviewed the records of 25 patients who had undergone PVP using a 120-W HPS in our institution. Patients were evaluated pre-operatively, and at 2 weeks and 1, 3, and 6 months postoperatively. RESULT: The mean age was 73.6 years, and the mean estimated preoperative prostate volume was 51.5 ml. Laser vaporization was performed successfully in all 25 patients. The operating time was 104 +/- 29 minutes. The mean decrease in hemoglobin was 0.6 g/dl on post-operative day 1. The International Prostate Symptom Score (IPSS), QOL score, maximum flow rate, and residual urine volume were significantly improved 2 weeks after the procedure. There were no serious complications during the peri-operative period, and no patients were transfused. CONCLUSION: PVP using a 120-W HPS was shown to be an effective, safe procedure for patients with BPH and lower urinary tract symptoms.

[Clinical study of 62 patients with symptoms of male climacterium].

We prospectively reviewed the records of 62 patients who had sought evaluation at our hospital with a chief complaint of male climacteric symptoms. Late-onset hypogonadism (LOH)-related symptoms were evaluated during the initial visit based on the Aging Males' Symptoms (AMS) score, International Index of Erectile Function (IIEF) -5 score, and Center for Epidemiologic Studies Depression Scale (CES-D). Laboratory and endocrinologic testing, including the free testosterone (FT) level, was performed with blood samples collected before 10 : 00 am. The AMS psychological and CES-D scores in patients with a FT ＞8.5 pg/ml were significantly higher than those in patients with a FT ≦8.5 pg/ml. The study included 32 patients who were diagnosed with LOH (FT ≦8.5 pg/ml) and treated with androgen replacement therapy (ART). The total, somatic, psychological, and sexual scores of the AMS were significantly decreased after the third intramuscular administration of testosterone enanthate; there were no serious complications. Because a significant proportion of depressed patients may be amongst the patients with aging male's symptoms, it is important to consider depression in the exclusion diagnosis during a clinical examination for LOH.

[A case of primary malignant lymphoma of the prostate with characteristic MRI findings].

Here, we report a case of malignant lymphoma (ML) of the prostate. A 77-year-old man was referred to our hospital with the chief complaint of left lumbago. Computed tomography imaging showed a large mass below the bladder, as well as left hydronephrosis resulting from infiltration of the mass. Magnetic resonance imaging (MRI) revealed enlargement and high-intensity of the whole prostate with diffusionweighted image. An enlarged, stony, hard prostate was palpable on digital rectal examination, but the prostate-specific antigen (PSA) level was 4.65 ng/ml. Since the patient developed urinary retention and macrohematuria, transurethral hemostasis and biopsy were performed. Histological findings and immunohistochemical studies revealed diffuse large B-cell non-Hodgkin's lymphoma (DLBCL). MRI is thought to play a critical role in localization diagnosis of Non-Hodgkin's lymphoma (NHL) since NHL demonstrates characteristic signs. Although the frequency of primary ML of the prostate is low, by paying careful attention to the characteristic signs on MRI and examination findings, we should consider a differential diagnosis of ML of the prostate, which is not a typical manifestation of prostatic cancer.

Limited expression of cancer-testis antigens in renal cell carcinoma patients.

The aim of this study was to evaluate the frequency of expression of the cancer-testis antigens (CTAs) NY-ESO-1, MAGE-A4 and SAGE, in renal cell carcinoma (RCC) patients compared to that in head and neck cancer (HNC) patients, which represent a positive control with a high incidence of CTA expression, to identify novel target antigens for immunotherapy. We prospectively examined frozen tissue samples collected from surgery or biopsy from 35 RCC and 40 HNC patients. Total RNA was extracted, and real-time reverse transcription-polymerase chain reaction (RT)-PCR was performed to determine the expression of MAGE-A4, NY-ESO-1 and SAGE. MAGE-A4 was not detected in any of the RCC samples, although a low incidence of NY-ESO-1 (5.7%; 2/35) and SAGE (2.9%; 1/35) expression was observed. No samples demonstrated co-expression of the three CTAs. By contrast, a comparatively high incidence of CTA expression was detected in squamous cell carcinoma (SCC) specimens of HNC patients. The actual incidence was 42.5% (17/40) for MAGE-A4, 20% (8/40) for NY-ESO-1 and 15% (6/40) for SAGE. The incidence of co-expression was 7.5% (3/40) for MAGE-A4 and NY-ESO-1, 7.5% (3/40) for MAGE-A4 and SAGE, 7.5% (3/40) for NY-ESO-1 and SAGE, and 2.5% (1/40) for the CTAs. The number of HNC samples positive for MAGE-A4 was significantly higher compared to that of RCC samples. The remaining two antigens, NY-ESO-1 and SAGE, were expressed at high levels in HNC compared to RCC samples. Limited frequency of CTA (NY-ESO-1, MAGE-A4 and SAGE) expression was demonstrated in RCC compared to HNC samples.

Manserin as a novel histochemical neuroendocrine marker in prostate cancer.

OBJECTIVES: To investigate the presence of manserin in human prostate cancers and to correlate manserin expression with pathologic outcomes and progression-free survival. METHODS: Eighty-seven patients with recent prostate cancer were classified into 4 groups based on Gleason score, and manserin immunohistochemistry was correlated with Gleason sum grade. To investigate the validity of manserin as a prognostic factor, the Cox proportional hazards regression model was performed on 48 patients in our cohort with T3 or T4 prostate cancer who were initially treated with androgen deprivation therapy. RESULTS: The manserin-positive rates of patients with Gleason sums of 6, 7, 8, and ≥9 were 0%, 20.0%, 35.0%, and 48.1%, respectively. Manserin-positive rates were positively correlated with Gleason sums (P = 0.0001). Median times to cancer progression in groups with (n = 8) and without (n = 40) manserin expression were 8 months and 28 months, respectively (P = 0.01). Univariate Cox analysis revealed that manserin expression, clinical stage T4, and high Gleason sum were significantly associated with progression. Multivariate analysis revealed that only 2 factors, manserin expression (hazard ratio (HR) 4.99, P = 0.01) and clinical stage T4 (HR 4.77, P = 0.03), were independent risk factors for progression. CONCLUSIONS: This is the first report of manserin expression in human prostate cancers. Manserin may serve as a marker of prostate cancer progression.